Vascular Biology

Blood vessels supply every organ in our body with blood and nutrients. They are also central to most diseases, especially the chronic inflammatory diseases. Our Vascular Biology program investigates the two main cells that form blood vessels – endothelial cells and smooth muscle cells.

Vascular leak is a hallmark of chronic inflammatory diseases, as well as the new blood vessels formed in cancer. Thus, an understanding of how vessels become leaky crosses all aspects of cancer, inflammation and cardiovascular disease. It is through this understanding that we are able to develop drugs that may inhibit or limit blood vessel leakiness.

Through our research, we have identified a molecule that is a ‘guardian of our arteries’ and protects us from the hardening of arteries, or atherosclerosis, the basis of heart attacks and strokes. We have also identified factors that can induce vascular leak, as well as factors that can inhibit vascular leak.

Finding a Cure

Using our understanding of how the vessel controls endothelial cell integrity, we have recently identified microRNAs (small junk-like DNA) that also play a critical role in changing cell junctions. These microRNAs are altered in disease and are good targets for the development of therapeutic drugs.

We have developed a first-in-class drug that is able to inhibit vascular leak and improve the outcomes of disease, as tested in pre-clinical models of peripheral ischaemia, tumour growth and eye disease.

There is an urgent need for drugs that specifically target vascular leak, as there are none on the market against this aspect of disease.

The development of an effective drug against vascular leak will have major impact on human health for a broad spectrum of diseases, including stroke, cancer, cardiovascular disease and eye disease.

Professor Jenny Gamble, Head of Program

Professor Jennifer Gamble is an internationally recognised research leader in the field of endothelial cell function and holds the Inaugural Wenkart Chair of the Endothelium.

Her interests lie in understanding endothelial cell function particularly in the area of inflammation, and how dysfunction can influence disease. Her initial publication in this area established the endothelium as a dynamic organ, central to the control of inflammatory processes.

The current studies in the Vascular Biology Program are under four broad areas:
1.understanding ageing of the endothelium and its impact on vascular function. Age is the greatest risk factor for the development of many diseases such as cardiovascular disease and cancer. Understanding the consequences of the ageing process to endothelial cell function will influence our ability to help us “age better”.

2. novel regulators of angiogenesis. Our genetic screens have identified genes that control endothelial cell function. One such gene impacts on tumour progression, metabolism and liver fibrosis. We are studying the mechanism of action of this gene, at the structural and functional levels

3.microRNA regulation of oedema and angiogenesis. MicroRNAs are small non-coding RNA, that control more than 30% of our protein coding genes. Thus they are known as regulators of major biological systems. Further they are often dysregulated in disease. Oedema is a critical feature in pathologies such as stroke and myocardial infarcts and angiogenic vessels in tumours are highly leaky. Limiting oedema can result in improved outcomes. We have identified a suite of microRNAs than influence vascular oedema and these are being studied as possible therapeutic candidates. Some of these microRNAs also regulate angiogenesis.

4.diseases of the Aorta. This is within the newly established Agnes Ginges, Diseases of the Aorta Laboratory, headed by Dr Renjing Liu and was established in collaboration with Prof Richmond Jeremy, Royal Prince Alfred Hospital. Initially we are focussing on thoracic aortic aneurysms which affect 1:500 to 1:1000 people and which can result in sudden death. Our aim is to identify the molecular determinants of disease progression, using animal models and extensive archival human material, which will expose opportunities to influence disease outcome.

Agnes Ginges Laboratory for Diseases of the Aorta

Cardiovascular disease is a major cause of morbidity and mortality worldwide. Many cardiovascular diseases, such as atherosclerosis, are largely caused by the dysfunctional regulation of smooth muscle cells, the principle cell type found in blood vessel walls. We have identified a new stem cell mediated pathway in the regulation of smooth muscle cells. Identifying effectors that target this new pathway has clear implications to treat cardiovascular diseases and will lead to the development of novel therapeutics.